The present invention relates to a method for manufacturing placebo tablets or positive control tablets, that are identical to tablets that contain active drugs. Clinical studies to determine the effectiveness of new drugs requires that identical tablets be prepared which contain an active drug, no drug (placebo) and/or a control drug. This is done in order to prevent the patients and investigators from knowing who is receiving the drug that is being tested and for this reason the clinical studies are usually referred to as being "double blind". This is because neither the investigator nor the patient can tell from the packaging which dosage form is the new drug.
In the prior art when a drug manufacturer carried out a test of a product against a competitor's patented product, it was not unusual to request that the competitor prepare a blinded supply of the product. This would usually be done if the study protocol and results were shared with the competitor.
In the prior art, blinded samples have been prepared by over encapsulation, coating or debranding. Over encapsulation is a process whereby a dosage form, which is usually a tablet, is placed in a capsule. This procedure requires in some cases the use of an oversize capsule which may be difficult to swallow. This process is time consuming and strict quality controls are required to assure that the capsule and tablet are bioequivalent and are manufactured properly. The gelatin and moisture in the capsules may introduce stability problems. Overcoating of tablets has not been successful for embossed tablets because of the formation of ghost images in the areas where the tablets are embossed. The debranding of printed tablets and capsules is a labor intensive process that may raise the question of stability due to the use of solvents for manually deinking the printed matter on the dosage form.
When compendium products are involved, a generic formulation may have to be prepared which requires a development project where stability and bioequivalence have to be demonstrated.
A further alternative is a mill and fill process where tablets are milled and filled into capsules. This procedure maximally disturbs the original dosage form and questions relative to equivalence uniformity, stability and bioavailability must be resolved.
The applicant has devised a process of coating branded dosage forms which does not compromise the integrity of the branded pharmaceutical dosage form but provides an overcoat that is sufficient to cover all product indicia without interfering with the stability or the releasability of the drug.
The invention also provides a method for coating micro tablets for the purpose of "rounding" the micro tablets to facilitate the mechanical filling of the micro tablets into capsules; a method of isolating incompatible ingredients in micro tablets and a method of incoporating an additional active ingredient into the micro tablet. As used herein a micro tablet is a tablet which is generally considered to be less than 4 mm in diameter (if round) or less than 4 mm in longest dimension. They are prepared with the same ingredients as traditional tablets and capsules which include lactose, starch, microcrystalline cellulose, disintegrants, flow agents and lubricants.